Prolonged in vivo hypoxia enhances nitric oxide synthase type I and type III gene expression in adult rat lung

Prolonged hypoxia in the adult rat causes a decline in endothelium-derived nitric oxide (NO) production in the pulmonary circulation. To evaluate whether this is related to a decrease in endothelial NO synthase (NOS-III) expression, we determined the effects of hypobaric hypoxia (7 or 21 days) on NO...

Full description

Saved in:

Bibliographic Details
Published in:	American journal of respiratory cell and molecular biology Vol. 13; no. 2; p. 167
Main Authors:	Shaul, P W, North, A J, Brannon, T S, Ujiie, K, Wells, L B, Nisen, P A, Lowenstein, C J, Snyder, S H, Star, R A
Format:	Journal Article
Language:	English
Published:	United States 01-08-1995
Subjects:	Amino Acid Oxidoreductases - genetics Amino Acid Oxidoreductases - metabolism Animals Base Sequence Blotting, Northern Disease Models, Animal Endothelium - enzymology Gene Expression - physiology Hypoxia - enzymology Hypoxia - physiopathology Immunoblotting Lung - cytology Lung - enzymology Male Molecular Sequence Data Nitric Oxide Synthase Polymerase Chain Reaction Rats Rats, Sprague-Dawley RNA, Messenger - metabolism Time Factors
Online Access:	Get more information
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Prolonged hypoxia in the adult rat causes a decline in endothelium-derived nitric oxide (NO) production in the pulmonary circulation. To evaluate whether this is related to a decrease in endothelial NO synthase (NOS-III) expression, we determined the effects of hypobaric hypoxia (7 or 21 days) on NOS-III gene expression in adult rat lung. Neuronal NOS (NOS-I) expression was also examined; NOS-I has been immunohistochemically localized to rat bronchiolar epithelium. NOS-III and NOS-I mRNA abundance were assessed in reverse transcription-polymerase chain reaction assays and the proteins were evaluated by immunoblot analysis. After 7 and 21 days of hypoxia, there were increases in the steady-state levels of both NOS-III and NOS-I mRNA, rising 2.7- to 3.0-fold and 2.5- to 2.8-fold, respectively. These findings were confirmed by Northern analyses. In parallel, NOS-III and NOS-I protein abundance were also increased with hypoxia by 3.0- to 3.5-fold and 2.4- to 3.0-fold, respectively. NOS activity detected by [3H]arginine to [3H]citrulline conversion rose 109%. Thus, prolonged in vivo hypoxia causes enhancement of NOS-III and NOS-I gene expression in adult rat lung, indicating that the pulmonary expression of these genes is modulated in vivo. The increase in NOS-III expression does not explain the declines in pulmonary endothelial NO production previously observed following prolonged hypoxia in this model. Alternatively, the fall in NO production may be related to diminished NOS co-factor availability.
ISSN:	1044-1549
DOI:	10.1165/ajrcmb.13.2.7542896